3 - Pharmacokinetics

Question 1

Define pharmacokinetics

Answer 1

• What the body does with the drug
• Movement of the drug within the body

Question 2

Define pharmacodynamics

Answer 2

• What drug does to the body
• Body’s response to the drug

Question 3

What are the factors that allow drugs to work?

Answer 3

• Must be in the right place
• Must be at the right concentration
• Must be in body for the right amount of time
• Has to be the correct dose

Question 4

What makes a dosage the correct dose?

Answer 4

There are no undesired or dangerous side effects

Question 5

What is ADME?

Answer 5

Absorption, distribution, metabolism, elimination

Question 6

What is the difference between absorption and adsorption?

Answer 6

Absorption - transfer into another substance
Adsorption - transfer onto another substance (on the surface)

Question 7

Under what circumstances does absorption occur in the a) gut wall, b) blood and c) oral mucosa?

Answer 7

a) Extravascular administration (e.g. oral)
b) Intravascular administration
c) Buccal administration

Question 8

Where does ADME occur?

Answer 8

A - Gut wall and blood
D - Body tissues
M - Liver
E - Kidneys

Question 9

How is the drug transported in the blood?

Answer 9

• Filtration through pores
• Passive diffusion (pass through membrane, no ATP)
• Active transport (pass through ion channels, ATP)
• Facilitated diffusion (pass through ion channels, no ATP)
• Phagocytosis - cells ‘eat’ drug
• Pinocytosis - cells ‘drink’ drug

Question 10

What happens during oral administration? E.g. swallowing a tablet

Answer 10

• Drug dissolved in gastric juices
• Drug mainly absorbed in small intestine, diffuse into hepatic portal vein
• Drug acidic? Unionised & absorbed in stomach & small intestines
• Drug basic? Travel to liver via hepatic portal system
• Drugs metabolised in liver -> sent to right side of heart -> lungs -> left side of heart -> enters circulatory system

Question 11

What happens during inhalation administration? E.g. smoking

Answer 11

Drug enters lungs -> diffuses into blood stream from alveoli -> enters left side of heart -> enters circulatory system

Question 12

What happens during intravenous administration? E.g. injecting

Answer 12

Drug enters circulatory system immediately

Question 13

What happens during transdermal administration? E.g. patch

Answer 13

Drug diffuses into skin -> diffuses into blood & enters circulatory system

Question 14

Define bioavailability

Answer 14

How much of the drug reaches systemic circulation

Question 15

Define first pass metabolism/effect

Answer 15

How much drug is metabolised before reaching systemic circulation

Explanation:
all drug absorbed in GI tract -? goes to liver via hepatic portal vein -> some drug metabolised

Question 16

What are the factors affecting distribution?

Answer 16

Main:
- Chemical structure of drug
- Route of administration
- Presence of food in GI tract
- Rate of blood flow

Additional:
- Membrane permeability
- Blood perfusion (passage from blood to organs/tissues)
- Lipid solubility (high water solubility means cross blood/brain barrier faster, high lipid solubility causes drugs to be stored in fats so higher dosage needed. More fat on a person = higher dosage of drug)
- Plasma protein
- Intracellular binding
- pH

Question 17

Where and how does metabolism take place?

Answer 17

Liver, broken down by P450 enzymes

Question 18

Define metabolism and its purpose

Answer 18

• Biochemical modification/degradation of a drug through enzymatic action
• Make a drug more polar to allow for easy and quick elimination (urine)
• Production of metabolites

Question 19

What is phase 1 metabolism? List the processes

Answer 19

• Non-synthetic reactions. Result in active/inactive drug
• Hydrolysis e.g. cocaine
• Oxidation e.g. atropine
• Reduction e.g. flunitrazepam
• Dealkylation e.g. codeine
• Deacetylation e.g. heroin

Question 20

What is phase 2 metabolism? List the processes

Answer 20

• Synthetic reactions or conjugation. Usually results in inactive drug, but an exception is morphine-6-conjugate (active metabolite of morphine)
• Sulphation (+ sulphur group, makes water soluble)
• Glucuronidation (+ glucuronic acid, make water soluble)
• Acetylation (+ acetyl group)
• Amino acid conjugation (+ amino acid, make water soluble)

Question 21

Name the different ways drugs are eliminated from the body

Answer 21

Air (expiration) - pulmonary
Faeces - bile (lipid-soluble substances)
Urine - renal (water-soluble substances)

Most drugs metabolised to water soluble substances

Question 22

What is the hepatic portal system?

Answer 22

• Network of capillaries that carry blood from capillaries in stomach, intestine, spleen and pancreas to those in the liver
• Filtration system
• Deliver deoxygenated blood to liver to be detoxified before going to heart

Question 23

What is the Cmax and tmax

Answer 23

Cmax - maximum concentration of drug
tmax - time of maximum concentration

Question 24

What is the equation for volume of distribution?

Answer 24

= total amount of drug present/concentration of blood plasma

Question 25

What is half-life (t1/2)?

Answer 25

Time it takes for the drug plasma concentration to halve

Question 26

What is ED50?

Answer 26

Concentration of drug that produces the desired therapeutic effect in 50% of the population

Question 27

What is TD50?

Answer 27

Concentration of drug which produces a toxic effect in 50% of the population

Question 28

What is the equation for blood alcohol concentration?

Answer 28

= total alcohol consumed-amount of alcohol metabolised/volume of distribution

Question 29

Name the analytical techniques involved in urine drug testing?

Answer 29

• Colour test
• Immunoassays
• TLC
• GLC
• GC/MS
• GC/IR